The primary objective of this study is to determine that pramipexole (Sifrol) 0.25 mg to 0.75 mg daily is not inferior to levodopa 100 mg to 300 mg (in combination with benserazide 25mg to 75mg = Madopar DR) daily in the treatment of patients with idiopathic restless legs syndrome fulfilling the International Diagnostic Criteria. The efficacy parameters include an objective measure of the leg movements during the time spent in bed, and a quantitative clinical assessment of the severity of RLS, in the form of the RLS-score. In addition, the efficacy evaluations aim at comparing the impact of pramipexole and levodopa on outcome measures such as quality of life and sleep.

Condition	Intervention	Phase
Restless Legs Syndrome	Drug: levodopa in combination with benserazide  Drug: pramipexole	Phase III

Further Study Details: 

Primary Outcomes: The primary endpoint will be the frequency of periodic limb movements while in bed (PLM-Index), as assessed over 3 consecutive nights at the end of the two treatment periods by actigraphy performed on two legs.
Secondary Outcomes: Efficacy: - Change in RLS-score - Sleep quality - Change in SF-36 scale, Hospital Anxiety and Depression Scale (HAD), Clinical Global Impression (CGI), Epworth Sleepiness Scale Safety: - AEs, Potential adverse drug reactions - Domperidon needs - Lab
Expected Total Enrollment:  40

This is a national, multi-centre study in adult patients with RLS. It will be conducted according to a randomised double-blind 2-sequence, 2-period crossover design. The duration of the study for individual patients is of approximately 14 weeks.

At the beginning of the two treatment periods, the dose will be one capsule per day of the double-blind medication, containing either 0.25 mg pramipexole or 100mg/25mg levodopa/benserazide. The subsequent dose adjustments should aim at determining the optimal dose, i.e. the dose at which a patient is in a satisfactory clinical state that cannot be improved by a dosage increase without eliciting relevant side effects.

Each of the four actigraphic measurements will be obtained over three consecutive nights from the two legs. The patient will start the recordings in the evening before going to bed and stop it after standing up in the morning.

Variables obtained from questionnaires regarding the clinical conditions of the patients are chosen as secondary efficacy variables. In contrast to the primary endpoint, these include subjective judgments by the patient or clinician. The change in the scores or the values from baseline will be compared for the two treatments.

Study Hypothesis:

The hypothesis of non-inferiority of pramipexole compared to levodopa.

Comparison(s):

The efficacy parameters include an objective measure of the leg movements during the time spent in bed, and a quantitative clinical assessment of the severity of RLS, in the form of the RLS-score. In addition, the efficacy evaluations aim at comparing the impact of pramipexole and levodopa on outcome measures such as quality of life and sleep.

Ages Eligible for Study:  25 Years   -   85 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion criteria:

• Patients diagnosed with idiopathic restless legs syndrome fulfilling the International Diagnostic Criteria 1 .
• Male or female patients, aged 25 to 85 years.
• Patients presenting RLS symptoms almost every day, as judged by the investigator and with more than 5 PLM/h during bedtime in each of three screening actigraphy nights.
• Patients must have given written informed consent in accordance with ICH- GCP and local legislation prior to participation in the study.

Exclusion criteria:

• Patients with significant diseases other than restless legs syndrome will be excluded. A significant disease is defined as a disease that, which in the opinion of the investigator may put the patient at a risk because of the participation in the study, that may influence the result of the study or the patient''''s ability to participate or that is expected to relevantly reduce life expectancy.
• Patients with known hypersensitivity or contraindications to pramipexole, levodopa or benserazide or any other substances present in the study medications.
• Patients with iron-deficiency
• Patients with disabilities or other incapacities that preclude regular attendance at clinic for the study visits, and patients on a shift-work-schedule or who are otherwise unable to follow a regular sleep-wake cycle.
• Patients who have been previously treated with pramipexole or levodopa.
• Pregnant or nursing women or women of childbearing age who are at risk of pregnancy and are not willing to use adequate contraceptive methods (hormonal contraception or intrauterine devices) during the study period.

Please refer to this study by ClinicalTrials.gov identifier  NCT00144209

Roland Stechert, Dr.      +41 (61) 2952-561  Ext. 561    roland.stechert@bas.boehringer-ingelheim.com

Switzerland
      Universitätsspital Zürich, ZÜRICH,  CH-8091,  Switzerland; Recruiting
      Inselspital, Bern,  3000,  Switzerland; Recruiting
      Laboratoire de Sommeil, Chêne Bourg, Genève,  CH-1225,  Switzerland; Recruiting
      Universitätsspital Basel, Medizinische Poliklinik, Basel,  4031,  Switzerland; Recruiting
      Klinik für Schlafmedizin, Zurzach,  5330,  Switzerland; Recruiting
      Klinik für Schlafmedizin, Luzern,  6006,  Switzerland; Recruiting
      Zentrum für Schlafmedizin, Basel,  4025,  Switzerland; Recruiting
Switzerland, CH
      Ospedale Regionale, Lugano,  CH,  CH-6903,  Switzerland; Recruiting

Study chairs or principal investigators

Roland Stechert, Dr.,  Study Chair,  B.I. Schweiz GmbH.   

Study ID Numbers:  248.518
Last Updated:  September 2, 2005
Record first received:  September 2, 2005
ClinicalTrials.gov Identifier:  NCT00144209
Health Authority: Switzerland: Swissmedic
ClinicalTrials.gov processed this record on 2005-09-06